1. Field of the Invention
The present invention relates to a composition preventing tissue adhesion and a method for preparing the same, and, more particularly, a composition preventing tissue adhesion which further contains a drug selectively inhibiting inflammatory response and a method for preparing the composition, in which the composition is produced through a chemical reaction by adding a cross-linking agent to an aqueous solution which contains a block copolymer containing a polyethyleneoxide block having the ability to suppress tissue adhesion, and a polymer with 10,000 to 1,000,000 g/mol of molecular weight which can be mixed with the copolymer; the composition is characterized in that the difference of viscosity, absorbance of visible rays region, and stability between the upper and lower liquid layers are within 10% when centrifuging the composition; and also the method for preparing the composition enhances cross-linking homogenization and viscosity stability through simultaneous spraying and stirring methods without a reaction retardant.
2. Description of Related Art
An adhesion is causing after various surgeries and is more strongly created by making tissue through a penetration of cell after making a first adhesion with surroundings organs or tissues from the effusion and coagulation of blood during the cure period of wound, such as an inflammation, a cut, a friction, a cut by a surgery, and the like. When generating an adhesion on a pelvis, a chronic pain, a sexual dysfunction, a sterility, and the like may be caused; the adhesion caused by a cicatrization after removing a thyroid causes a side effect, such as a chest pain, a decline of swallow ability, and the like; and the adhesion caused by spine surgery causes a sharp pain due to a neurothlipsis. Therefore, a second surgery may be required for removing the adhesions as mentioned above so that the financial burden has been increased and it is reported that the cost used for treating complications due to the adhesion after an adnominal operation is about 12 hundred million according to USA statistical data in 1988. It is known that a closure of small intestine is about 49 to 74%, sterility is about 15 to 20%, a chronic pelvis pain is about 20 to 50%, and an enterobrosis on a following surgery is about 19% as the complications caused by the adhesion after an abdominal operation. In addition, a recurrence rate is about 7.6 to 38% of patients after an endoscopy of the nasal cavity for treating a chronic sinusitis of an ear-nose-throat department. Also, it is reported that according to ‘Ramadan’ Thesis disclosed on Laryngoscope Journal (Laryngoscope, Jan.; 109(1): p. 27˜29 (1999), Ramadan H. H., “Surgical causes of failure in endoscopic sinus surgery.”), the adhesion is generated in 56% of the patients that have a re-operation due to the above reason. In the case of gynecology, the adhesion in the endometrium is generated at 20 to 50% after a suction evacuation or an excochleation due to a defective miscarry, a stillbirth, a recurrent miscarry, and the like, and it is known that a sterility, an amenorrhea, a habitual abortion, and the like are caused by the above adhesion so that many researches are being carried out to prevent the adhesion. Currently, a method using a physical barrier is developed and then in use.
It is well known that for a polyethylene glycol-polypropylene glycol-polyethylene glycol (PEC-PPG-PEG) block copolymer, its state is changed due to heat, such that its viscosity is changed according to the response to the environment stimulation, such as acidity, a temperature, an ion capacity, and the like, and is increased from a solution state to a gel state. Therefore, the techniques for using as a material for medical using the above features are disclosed in U.S. Pat. No. 5,939,485, No. 4,188,373, No. 4,478,822, No. 4,474,751, and the like.
Korean Patent No. 10-2003-0050953 among the conventional techniques related to a preventing agent of tissue adhesion discloses using a high-speed stirrer to cross-link the copolymer giving a proper viscosity and stability in a liquid solution by using one or more cation selected from the group consisting of Mg2+, Ca2+, Sr2+ and Ba2+ and one or more selected from the group consisting of chitosan, glutaraldehyde, formalin, and poly-L-lysine, but floating debris on a fiber are generated when preparing in a mass production and it is hard to remove the floating debris and also to make even cross-linking.
Korean Patent No. 10-2006-0053279 discloses a method for making even cross-linking by adding one reaction retardant selected from the group consisting of sodium carbonate (Na2CO3), trisodium phosphate (Na3PO4), hydrated trisodium phosphate (Na3PO412H2O), sodium polyphosphate (Na5P3O10), tetrasodium pyrophosphate (Na4P2O7), hydrated tetrasodium pyrophosphate (Na4P2O710H2O), and hydrated ethylene diamine tetra acetic acid tetrasodium (Na4EDTA2H2O) as a reaction retardant for an ion-exchange polymerization, but the method is not suitable for a human body.
As mentioned above, it could not be prevented that the floating debris on a fiber generated due to uneven cross-linking up to now, and it could not be prepared that a composition preventing tissue adhesion can increase even cross-linking and stability of the viscosity.